A Study of IDN-6556 in Subjects With NAFLD and Raised Transaminases

Phase 2

Completed

• Conditions: Nonalcoholic Steatohepatitis; Non-alcoholic Fatty Liver Disease
• Interventions: Drug: IDN-6556; Other: Placebo

• Registration Number: NCT02077374
• Lead Sponsor: Conatus Pharmaceuticals Inc.

Brief Summary

The purpose of this study is to determine the safety and efficacy of IDN-6556 compared to placebo in patients with diagnosed fat deposits in their liver (not caused by alcohol) and with abnormal liver tests

Detailed Description

This is a double-blind, randomized study to evaluate the effects of IDN-6556 on serum transaminases and pharmacodynamics of IDN-6556 in subjects with non-alcoholic fatty liver disease with elevated alanine aminotransferase.

Study Timeline

• Study First Submitted: 2014-02-28
• Study Start: 2014-03
• Study First Submitted QC: 2014-03-03
• Study First Posted: 2014-03-04
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Results First Submitted: 2016-03-30
• Results First Submitted QC: 2016-06-09
• Status Verified: 2016-07
• Results First Posted: 2016-07-21
• Last Update Submitted: 2016-07-25
• Last Update Posted: 2016-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

• Male or female subjects of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the study
• Diagnosis of non-alcoholic fatty liver disease (NAFLD) as evidenced by imaging or other diagnostic assessments
• Alanine aminotransferase (ALT) levels ≥1.5 x ULN on at least two occasions, seven or more days apart, during the Screening period
• alpha-fetoprotein (AFP) ≤ 100 ng/mL
• Hemoglobin ≥10 g/dL, a platelet count ≥ 100 x 10^9/L, and a white blood cell count ≥ 3.0 x 10^9/L
• If on metformin, sulfonylureas, statins, or fibrates, subjects must be on a stable dose of these drugs for at least three months prior to Screening and during the study

Exclusion Criteria

• Known infection with HIV, HCV, or HBV

• Decompensated or severe liver disease as evidenced by one or more of the following:

  1. Confirmed cirrhosis or suspicion of cirrhosis
  2. Esophageal varices
  3. Ascites
  4. Suspicion of portal hypertension
  5. Hospitalization for liver disease within 60 days of screening
  6. Bilirubin >2 x ULN, or ALT or AST > 10 x ULN

• Inflammatory bowel disease

• Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA)

• Hepatocellular carcinoma (HCC) at entry into the study

• History of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)

• Significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal insufficiency, and/or serious psychiatric disease, that, in the opinion of the Investigator would preclude the subject from participating in and completing the study

• History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 4-ounce glasses of wine or 14 12-ounce cans/bottles of beer or wine coolers), or other substance abuse within the prior two years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IDN-6556	IDN-6556	IDN-6556 capsules, 25 mg BID
Placebo	Placebo	Placebo BID

Primary Outcome Measures

Name	Time	Method
Change in Alanine Aminotransferase (ALT)	Day 28/ET	Mean change in alanine aminotransferase (ALT) from Baseline to Day 28/ET between IDN-6556 vs Placebo
Relative Percent Change in Alanine Aminotransferase (ALT)	Baseline to Day 28/ET	Back transformation from log-transformed analysis results to original scale in alanine aminotransferase (ALT) from Baseline to Day 28/ET between IDN-6556 vs Placebo

Secondary Outcome Measures

Name	Time	Method
Levels of flCK18/M65	Day 28/ET	Difference in the change in full-length cytokeratin 18 (flCK18/M65) in units per liter (U/L) from Baseline to Day 28/ET between IDN-6556 and placebo
Change in Aspartate Aminotransferase (AST)	Day 28/ET	Difference in the change in aspartate aminotransferase (AST) from Baseline to Day 28/ET in units per liter (U/L) between IDN-6556 and placebo.
Levels of cCK18/M30	Day 28/ET	Difference in the change in Caspase-cleaved cytokeratin serum levels (cCK18/M30) in units per liter (U/L) from baseline to Day 28/ET between IDN-6556 and placebo
Levels of Caspase 3/7 RLU	Day 28/ET	Difference in the change of caspase 3/7 (Relative Light Units) from baseline to Day 28/ET between IDN-6556 and Placebo

Trial Locations

Locations (7)

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Mary Immaculate Hospital; 🇺🇸 Newport News, Virginia, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Mayo Clinic Rochester; 🇺🇸 Rochester, Minnesota, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Kansas City Research Institute; 🇺🇸 Kansas City, Missouri, United States

Bon Secours St. Mary's Hospital; 🇺🇸 Richmond, Virginia, United States